Hyperactive brain cells could be early hint of autism

Hyperactive brain cells firing together could be an early indicator of autism and developmental disabilities, a team of UCLA researchers has found.

Networks of neurons were found to be firing in a highly synchronized and seemingly unrelenting fashion, even through sleep, in the brains of juvenile mice that have a genetic abnormality similar to one that causes mental retardation and autism symptoms in humans, according to the research published online Monday in Nature Neuroscience.

Without independently firing neurons, the human brain would be about as functionally complicated as a digital switch. With it, we compose poetry and send robotic carts to Mars.

"If you want to code information, you can’t just have all the cells fire together or not, because then that’s just binary. It goes up and down," said UCLA neuroscientist Carlos Portera-Cailliau, a lead author of the report. “But if you have billions of neurons, all firing independently or in small clusters, then you can code a lot of information.”

That “de-synchronization” was greatly diminished in the neocortex of the juvenile mice that had been altered so that they lack the same protein known to cause mental retardation and autistic behaviors in humans.

These so-called Fmr1 Knockout mice, named for the gene that is knocked out, exhibit autism behaviors, among them social deficits – they don’t go over and sniff and examine a new mouse introduced to the cage, like wild mice would.

The researchers inserted a transparent panel in the skulls of the mice so they could put them under a sophisticated microscope that would reveal how neurons were firing.

"It looks like Christmas lights," Portera-Cailliau said.

But the Christmas lights of the young mice were still blinking away during sleep, a crucial time when the brain works on its database – consolidating memory, which is vital for cognition and behavioral response. And far more of the neurons fired in synchrony than would in a normal brain, the researchers found.

Neurons of humans fire synchronously in utero, but sometime before birth they begin to fire independently. “This transition is really important,” Portera-Cailliau said. "If you don’t have this transition then computations in the brain are going to be abnormal.”

Scientists have been making slow inroads toward the neurobiological roots of autism, which is characterized by deficits in social interaction and communication and a restriction of interests that often comes with repetitive behavior.

Studies have shown some circuits appear to be “over-wired,” while others appear to lack appropriate connections. Those somewhat contradictory traits are merging in a theory that suggests local circuits may be overwrought while longer connections are mis-wired.

By that theory, neuron-level misfires could make one aspect of the brain’s processing more sensitive, such as vision or touch, yet thwart more complex connections. Studies have shown an abundance of misaligned brain activity between autistic and typically developed brains both at a network and neuron level.

At the same time, scientists have been digging for a genetic cause to the disorder and its link with Fragile X syndrome. For instance, in Fragile X syndrome, parts of neurons are abnormally long and thin, just as they are among low-IQ autistics. This suggests a common mechanism could be at the root of both.

The genetic research has been promising, Portera-Cailliau said. “But it’s a big leap to go from a gene defect to abnormal behavior. We wanted to bridge that gap and study the circuit, because ultimately it’s easier to link an abnormal circuit in the brain to an abnormal behavior."

Such a link could lead to a drug that might affect the rapid and synchronous firing of neurons, and possibly help calm or de-synchronize them while the brain is still maturing. It would not be a cure but could be a powerful intervention, Portera-Cailliau said.

In the meantime, the UCLA team will probably start examining the link between the abnormal network connections and learning impairment. And the bigger step will be to find ways to test the theory in human brains.